Sodium channels play a diverse set of roles in maintaining normal and pathological states, including the long-recognized role that voltage-gated sodium channels play in the generation of abnormal neuronal activity and neuropathic or pathological pain. Damage to peripheral nerves following trauma or disease can result in changes to sodium channel activity and the development of abnormal afferent activity including ectopic discharges from axotomised afferents and spontaneous activity of sensitized intact nociceptors. These changes can produce long-lasting abnormal hypersensitivity to normally innocuous stimuli, or allodynia. Examples of neuropathic pain include, but are not limited to, post-herpetic neuralgia, trigeminal neuralgia, diabetic neuropathy, chronic lower back pain, phantom limb pain, and pain resulting from cancer and chemotherapy, chronic pelvic pain, complex regional pain syndrome and related neuralgias.
PCT Published Patent Application No. WO 2006/110917, PCT Published Patent Application No. WO 2010/045251, PCT Published Patent Application No. WO 2010/045197, PCT Published Patent Application No. WO 2011/047174, PCT Published Patent Application No. WO 2011/002708 and PCT Published Patent Application No. WO 2013/154712 disclose certain spiro-oxindole compounds which are useful as voltage-gated sodium channel inhibitors and therefore useful in treating diseases and conditions which are associated with voltage-gated sodium channel activity, particularly the activity of sodium channel NaV1.7.
One of these spiro-oxindole compounds is funapide, which is also known as TV-45070 or XEN402. Funapide has the following structure:
and a chemical name of (S)-1′-{[5-(trifluoromethyl)furan-2-yl]methyl}spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one. Funapide is specifically disclosed in PCT Published Patent Application No. WO 2011/002708, which corresponds to U.S. Pat. No. 8,450,358, the disclosure of which is incorporated in full herein by reference.
Methods of preparing funapide and/or its racemate are disclosed, for example, in PCT Published Patent Application No. WO 2006/110917, PCT Published Patent Application No. WO 2011/047174 and PCT Published Patent Application No. WO 2013/154712. In particular, PCT Published Patent Application No. WO 2011/047174 discloses a method of preparing funapide by resolving its racemate by either SMB chromatography or by chiral HPLC and WO 2013/154712 discloses methods of preparing funapide by asymmetric synthesis.
There exists, therefore, a need for additional methods of preparing funapide which result in increased yields and purity of funapide than the methods previously disclosed.